|Year : 2019 | Volume
| Issue : 1 | Page : 36-44
A pilot study on neonatal surgical mortality: A multivariable analysis of predictors of mortality in a resource-limited setting
Archana Puri1, Brahmanand Lal1, Sushma Nangia2
1 Department of Pediatric Surgery, Lady Hardinge Medical College and Kalawati Saran Children's Hospital, New Delhi, India
2 Department of Neonatology, Lady Hardinge Medical College and Kalawati Saran Children's Hospital, New Delhi, India
|Date of Web Publication||19-Dec-2018|
Dr. Archana Puri
Type 4 Special Flats, Sector 12, Flat No. 1165, R. K. Puram, New Delhi - 110 022
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Purpose: The aim of this research is to study the predictors of neonatal surgical mortality (NSM)-defined as in-hospital death or death within 30 days of neonatal surgery.
Materials and Methods: All neonates operated over the study period of 18 months were included to evaluate NSM. The evaluated preoperative and intraoperative variables were birth weight, gestation age, age at presentation, associated anomalies, site and duration of surgery, intraoperative blood loss, and temperature after surgery. Assessed postoperative variables included the need for vasopressors, postoperative ventilation, sepsis, reoperations, and time taken to achieve full enteral nutrition. Univariate and multivariate logistic regression was applied to find the predictors of mortality.
Results: Based on patient's final outcome, patients were divided into two groups (Group 1-survival, n = 100 and Group 2-mortality, n = 50). Incidence of NSM in this series was 33.33%. Factors identified as predictors of NSM were duration of surgery >120 min (P = 0.007, odds ratio [OR]: 9.76), need for prolonged ventilation (P = 0.037, OR: 5.77), requirement of high dose of vasopressors (P = 0.003, OR: 25.65) and reoperations (P = 0.031, OR: 7.16 (1.20–42.81).
Conclusion: NSM was largely dependent on intraoperative stress factors and postoperative care. Neonatal surgery has a negligible margin of error and warrants expertize to minimize the duration of surgery and complications requiring reoperations. Based on our observations, we suggest a risk stratification score for neonatal surgery.
Keywords: Determinants, intraoperative stress, mortality, postoperative care, surgical neonates
|How to cite this article:|
Puri A, Lal B, Nangia S. A pilot study on neonatal surgical mortality: A multivariable analysis of predictors of mortality in a resource-limited setting. J Indian Assoc Pediatr Surg 2019;24:36-44
|How to cite this URL:|
Puri A, Lal B, Nangia S. A pilot study on neonatal surgical mortality: A multivariable analysis of predictors of mortality in a resource-limited setting. J Indian Assoc Pediatr Surg [serial online] 2019 [cited 2019 Jun 17];24:36-44. Available from: http://www.jiaps.com/text.asp?2019/24/1/36/247904
| Introduction|| |
Neonatal surgery, the epitome of paediatric surgery, is extremely challenging and has negligible margin of error. There is a wide global disparity in the reported neonatal surgical mortality (NSM) rates varying from 4% to 80%. Advances in pediatric anesthesia and airway management, a better understanding of transitional neonatal physiology, the establishment of neonatal intensive care unit (NICU), the introduction of total parenteral nutrition and effective treatment of infections led to improved neonatal surgical survival rates in developed countries. Poor antenatal care, delayed surgical referral, lack of NICU, limitations in trained workforce, and infrastructure are some of the contributory factors for high NSM in low resource countries like India. Most of the available literature on NSM is based on retrospective observational studies that have described preoperative determinants of NSM.,, However, overall NSM is determined by preoperative, intraoperative, and postoperative factors. The current study is an attempt to provide a holistic assessment of predictors of NSM by prospectively evaluating these factors and to develop a risk stratification score for neonatal surgery. This may help to prognosticate and stratify patients in different risk groups, to compare the performance of different neonatal surgical units for similar risk groups and to study the trends in results over time to see if there are any improvements in services.
| Materials and Methods|| |
This prospective observational study over a period of 18 months (December 2014–June 2016) included 150 surgical neonates undergoing thoracic, abdominal, and spinal surgeries. A surgical neonate was defined as a neonate who is either (i) born at >37 weeks of gestation (term neonate) and is <29 days at the day of surgery or (ii) born at <37 weeks of gestation (preterm neonate) and is <50 full weeks postconception at the time of operation. Postoperative neonatal referrals were excluded from the study. Preoperative, intra-operative and postoperative variables as described in [Table 1] were recorded by one observer (Brahmanand Lal). Each variable was scored in ascending order of severity from 0 to 2 to assign a preoperative, intraoperative, and postoperative score to each surgical neonate. Physiological parameters (heart rate, respiratory rate, urine output, and temperature) were evaluated within the first 2 h of admission to minimize the effect of treatment bias. Preoperative illness severity score (ISS) was assigned based on physiological parameters, pH and platelet count at presentation as shown in [Table 1]. ISS of 0–4 was be graded as 0, 5–8 as 1 and 9–12 as 2. The outcome variables were NSM (defined as in-hospital death or death within 30 days of neonatal surgery) and survival (documented at 1 month after discharge). The association of individual variable with the outcome (alive or dead) was tested using the Chi-square. Odds ratio (OR) and respective confidence intervals (CIs) were calculated for all the qualitative variables. Receiver operator characteristic (ROC) analysis determined the critical values of the quantitative variable to predict NSM. Variables found to be associated with adverse outcome were included for multivariate backward elimination analysis to find the predictors of mortality. P < 0.05, 95% CI was considered statistically significant.
|Table 1: Numerical grading of preoperative, intraoperative and postoperative variables|
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| Results|| |
Based on the patient's outcome (survival and mortality), patients were divided into two groups (Group 1-survival, n = 100 and Group 2 mortality, n = 50). The incidence of NSM in this series is 33.33%. Distribution of disease, preoperative, intraoperative, and postoperative variables in the two groups are shown in [Table 2], [Table 3], [Table 4], [Table 5]. There was a male preponderance with a sex ratio of 3:2. The mean age of presentation in this series was 9.6 ± 2.46 days. Majority of our patients (n = 95, 63.33%) presented within 7 days of life, however, 21.9% had delayed presentation beyond 15 days. Most common neonatal surgical diseases were esophageal atresia (EA, n = 43; 28.66%) followed by anorectal malformation and necrotizing enterocolitis (NEC, n = 22 each; 14.6%) and small bowel atresia [Table 2]. The overall NSM in EA in this series was 53.48% and accounted for 46% of the total mortality. Mortality in congenital diaphragmatic hernia (CDH) occurred in four patients with persistent pulmonary hypertension. NEC with bell's stage III had 100% mortality in very preterm and very low birth weight (VLBW) neonates (n = 18), with pan-NEC (4.5%) and in those with leak requiring re-exploration (4.5%). NEC perforation was the 2nd most common cause of mortality. Duodenal atresia was the common site of small bowel atresia followed by ileum and jejunum (43.7%, 31.2%, and 25%, respectively). The mortality rate in the three types was 14.28%, 20% and 70%, respectively. Overall mortality in small bowel atresia in this series was 31.2%. Most of the mortality in small bowel atresia was seen in patient with jejunal atresia (75%), babies requiring re-exploration (18.3%) and in babies <2 kg.
|Table 4: Distribution and analysis of intraoperative variables in the 2 grou|
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|Table 5: Distribution and analysis of postoperative variables in the 2 groups|
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The mean birth weight in Group 1 was 2.45 ± 0.49 kg as compared to 2.08 ± 0.59 kg in Group 2 (P = 0.001). Birth weight of <2 kg increased the odds for mortality by 3.41 times (95% CI: 1.62–7.15). However, the area under the ROC curve was 0.67 (95% CI: 0.58–0.766) suggesting a positive but weak association between birth or admission weight and NSM.
Majority of our babies (n = 92; 61.33%) were term neonates (>36 weeks) while 38 (25.33%) were preterm (32–36 weeks) and 20 (13.33%) were very preterm. NSM in term, preterm, and very preterm neonates was 22.6%, 50%, and 65%, respectively. Prematurity of <36 weeks increases the odds of mortality by 3.38 times (95% CI: 1.67–6.87). The area under the ROC curve was 0.68 (95% CI: 0.58–0.77) suggesting a positive but a weak association between gestational age and mortality. Age at presentation, sex distribution, and place of delivery failed to show significant correlation with NSM.
Other associated anomalies
Major congenital anomalies were defined as life-threatening anomalies or duct dependent congenital heart diseases. In this study, major congenital anomalies were noted in 13 patients of whom 7 (53.84%) expired. Of the 94 patients with no or minor congenital anomalies 3 (3.19%) expired (P < 0.001). However, associated anomalies could not be assessed in 40 (26.66%) cases that died soon after admission or were too sick to be shifted for investigations.
Illness severity score
Although mean ISS in the two groups did not vary significantly, yet patients with ISS >5 had 21.64 times higher risk of mortality (P = 0.000). The area under ROC curve was 0.604 (95% CI: 0.504–0.705) suggesting a positive but a weak association with NSM. ISS ≥5 in neonates with birth weight <2 kg and gestational age <32 weeks (n = 10) had 90% mortality. Moreover, delayed presentation of >48 h with ISS ≥5 (n = 12) had 66.67% mortality.
Systemic infection with positive blood cultures were present in 19 patients of whom 84.2% expired, while those with negative cultures had mortality of 25.9% (P = 0.000, OR = 16.94, 95% CI = 4.54–59.86). Infection with Gram-negative, Gram-positive and fungal organism were seen in 16 (84.2%), 2 (12.5%) and in 1 patients, respectively. Other cultures, namely, endotracheal tube, wound, and urine were positive in 8 patients of whom 4 (50%) expired.
Duration of surgery
Duration of surgery was recorded from incision time to closure to evaluate surgical stress in neonates. Although, mean duration of surgery in the two groups did not vary significantly [Table 4]; yet on univariate analysis duration of surgery >120 min showed positive correlation with NSM (P = 0.000) and increased the odds for mortality by 9.28 times (95% CI: 2.95–29.24).
Intraoperative blood loss was expressed as a percentage of total blood volume. Blood loss of >10% increase the odds for mortality by 21.67 times.
Site of surgery
Intra-thoracic surgeries constituted 50% of the total mortality followed by abdominal in 44%. In this series intra-thoracic surgery in newborns increased the odds for mortality by 5.26 times (95 CI: 1.30–21.32), especially in those who required preoperative and postoperative ventilation.
Temperature after surgery
Based on intraoperative temperature hypothermia was graded as mild, moderate, and severe with mortality rates of 21.4%, 43%, and 100%, respectively (P = 0.003).
Extubation after surgery
The need for postoperative ventilation showed a positive correlation with NSM. The mortality rate varied significantly among those who did not require postoperative ventilation (9.27%), required for <24 h (22.22%) and >24 h (88.63%, P = 0.000). In this study postoperative ventilator requirement for <24 h and >24 h increased the odds for mortality by 2.79 and 76.27 times, respectively.
Hemodynamic instability requiring higher dose of dopamine and dobutamine with adrenaline was associated with significantly higher NSM (P = 0.000). The mortality rate according to the use of inotropes was 10%, 15%, and 92.5% in those with no, low and high dose of inotropes, respectively.
Major complication requiring reoperations was associated with 77.7% mortality and increased the odds for mortality by 16.40 times (P = 0.000).
Time to full enteral nutrition
Meantime taken to achieve full enteral nutrition did not vary significantly between the 2 groups (Group 1: 8.54 ± 5.46; Group 2: 8.19 ± 4.35 days). Based on time taken to achieve full enteral nutrition in <7, 7–14, >14 days; NSM was 28.7%, 23%, 73%, respectively (P = 0.000).
Comparison of preoperative, intraoperative, postoperative scores, and length of hospital stay in the two groups
In this study, numerical graded scores were assigned to preoperative (0–12), intraoperative (0–8), and postoperative variables (0–10). Preoperative scores in the two groups did not vary significantly (Group 1: 3.62 ± 1.48; Group 2: 4.78 ± 1.86). Mean intraoperative scores in the two groups was 3.63 ± 2.2 and 6.58 ± 2.4, respectively, median intraoperative score of survivors was much lower than the nonsurvivor (4 vs. 7, P ≤ 0.001). Mean postoperative scores were significantly different in the two groups with survivors having median of 1.18 ± 1.5 and nonsurvivor 5.48 ± 2.8. Mean length of hospital stay in the two groups varied significantly (Group 1: 11.17 ± 7.18; Group 2: 8.56 ± 12.13 days, P = 0.000), The nonsurvivors had a shorter median length of hospital stay of 4 days as compared to 10 days in survivors, suggesting an early mortality within first few days of surgery. Length of hospital stay varied from 2 to 34 and 0–65 days in Group 1 and 2, respectively. The area under the ROC curve for preoperative, intraoperative, postoperative scores, and length of hospital stay was 0.694, 0.816, 0.912, and 0.708, respectively, suggesting a significant strong positive association of intraoperative and postoperative scores with NSM [Figure 1].
|Figure 1: Median preoperative, intraoperative and postoperative scores in the 2 groups and receiver operator characteristic of the length of hospital stay|
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Multivariate backward logistic regression analysis
The variables which were retained in the final model were duration of surgery >120 min, need of prolonged ventilation, requirement of high dose of vasopressors, and need for reoperations. These four factors were found to be the predictors of mortality as shown in [Table 6]. Duration of surgery >120 min especially in low birth weight (LBW), preterm babies with ISS >5 increased the odds of mortality by 9.76 times. Prolonged need of ventilation and higher dose of vasopressors increased the odds for mortality by 5.77 and 25.65 times, respectively.
| Discussion|| |
Neonatal mortality rates are a reflection of medical care in a particular country. Nearly 10% of neonatal deaths are due to congenital malformations requiring surgical intervention. Thus, NSM contributes significantly to neonatal mortality. Reported NSM shows a geographical variation from 4% in USA, 6%–7% in Japan, 35%–45% in India, 52.7% in Uganda and 62.2% in Nigeria.,,,, NSM in this series was 33.3% which is accordance with that reported earlier from India but is much higher than <5% reported from developed countries.,,, NSM in developed countries is chiefly contributed by uncorrectable abnormalities of heart, lung, kidney, CNS, and inborn error of metabolism along with extreme prematurity and VLBW., Most of the previous studies have described preoperative (patients-related factors) as determinants of NSM.,,,, There are very few studies that have described intraoperative and postoperative determinants of NSM. In the present study, preoperative, intraoperative, and postoperative risk factors were recorded and were utilized to formulate the three composite numerical score. Although the preoperative score did not vary significantly, mean intraoperative and postoperative scores were significantly higher in nonsurvivors. This signifies that more or less patient characteristic was similar in the two groups and NSM in this study was largely dependent on intraoperative stress factors and postoperative care. Although, historically birth weight was a major prognostic factor for surgical newborns, yet of late there has been a lot of rethinking on the significance of birth weight as a stand-alone determinant of NSM. In most of the developed countries, it has become an obsolete parameter in the prognostic risk categorization as they are able to take care of LBW, VLBW, preterm, and SGA surgical newborns. However in developing countries LBW still remains an important determinant for NSM, as seen in this study where birth weight <2 kg was associated with 3.41 times higher probability of mortality. Similarly, prematurity of <36 weeks increased the risk of mortality by three and a half times. However, LBW and prematurity were not identified as predictors of NSM on multivariable analysis. Neonatal surgical conditions are associated with other congenital anomalies in 15%–50% of patients. In this study, babies with associated major congenital anomalies had a higher mortality rate (53.84%) as compared to those with no or a minor anomaly (3.19%), the association was statistically significant (P < 0.001).
Various neonatal ISSs such as Clinical Risk Index of Babies (CRIB), CRIB II, Score for Neonatal Acute Physiology - Perinatal Extension (SNAP) and SNAP-PE have been described in the literature., However, they have limited utility in surgical newborns. Currently described risk stratifications for surgical neonates are disease-specific like Waterston, Spitz, and Montreal for EA ± tracheoesophageal fistula, Nixon for small bowel atresia and Bell's staging for NEC.,, There is a need for risk categorization that can be applied to all surgical newborns irrespective of their disease. In this study, we used an ISS based on physiological parameters that were recorded within 2 h of admission. Although the mean ISS in the present study did not vary significantly between the survivors and nonsurvivors, yet patients with ISS ≥5 had 21.64 times higher risk of mortality as compared to those with ISS <5. In babies with ISS ≥5 a period of preoperative stabilization decreased intraoperative stress, helped to decrease the postoperative requirement of inotropes and ventilation and was associated with lower NSM. On the basis of our analysis, we identified two high-risk groups: (i) babies with birth weight <2 kg, gestational age <32 weeks and ISS ≥5 who had 90% mortality and (ii) babies with delayed presentation >48 h with ISS ≥5 who had 66.67% mortality.
A wide variation in age at presentation has been reported in the literature with spectrum varying from antenatal diagnosis to as late as the 3rd week of life as compared to 9.6 ± 2.46 days in this study.,,, Most of the studies, however, failed to shows a causal relationship between age at presentation, gender, delay in seeking treatment and NSM as was also the case in this study (P > 0.05). This is in sharp contrast to the observations by Osifo et al. who reported 65.5% mortality in neonatal surgical emergencies with delayed presentation of whom 7.5% were too sick on arrival and died during resuscitation. They described a three-delay model to explain the reasons for delayed hospital presentation. The first delay is in the identification of disease and in taking the decision to seek treatment, the 2nd delay is in the arrival to the hospital and a 3rd delay is in receiving adequate care at the hospital., In surgical newborns first and the second delay may contribute to hypothermia, fluid and electrolyte imbalance, infection and poor lung condition in patient of EA. This may lead to the opening of shunts and pulmonary hypertension in patients of CDH. This, in turn, leads to the 3rd delay as a variable period of resuscitations may be required before surgery. Delivery at home by untrained birth attendants and their inability to identify the disease may also contribute to first delay, infection, poor cord care, birth trauma, and unacceptably high mortality. However, the place of delivery failed to show any correlation with NSM in this series (P = 0.605). We hypothesize that those surgical newborns who were delivered at home or at level 1 probably died before arrival to the hospital constituting hidden mortality. There is enough scientific evidence to show that delivery at healthcare facilities significantly reduces neonatal mortality by 29% and the same should be the case for surgical newborns too. Moreover, of the 102 outborn surgical neonates in this series 34 (33.3%) had ISS of ≥5.
Neonatal stress response to surgery is the most important determinant of hormonal and metabolic changes following surgery which have a bearing on mortality and morbidity. In this study intraoperative stress factors as described by Anand and Aynsley-Green were used as intraoperative predictors of NSM. Duration of surgery is an important determinant of surgical stress, especially in neonates due to limited metabolic reserves and increased chances of hypothermia with prolonged procedures. The risk of hypothermia is maximal for abdominal wall defects, CDH (as the resultant metabolic acidosis leads to PPHN), gastroschisis, neural tube defects, LBW and preterm neonates. In this series, although mean duration of surgery in survivors and nonsurvivors was not significantly different, duration of surgery >120 min showed a positive correlation with NSM and increased the odds for mortality by >9 times, especially in LBW and preterm neonates. Moreover, blood loss of >10% of blood volume, hypothermia and major complications requiring reoperations were associated with significantly increased mortality and increased the odds for mortality by 21.67, 9.54, and 16.4 times, respectively. This emphasizes the need for developing expertise and special training for neonatal surgery to minimize the operating time, blood loss, and complications. Impaired neonatal respiratory physiology is an important risk factor for neonatal mortality and finds a mention in invariably all neonatal stress scores. In the present study, nearly one-third (33.33%) of neonates required postoperative ventilation and 29.33% required it for >24 h. The mortality varied significantly among those who did not require postoperative ventilation (9.27%), required for <24 h (22.2%) and those requiring >24 h (88.63%) (P = 0.000). Postoperative ventilation <24 h and >24 h increased the odds for mortality by 2.79 and 76.29 times, respectively. This is in accordance with Snajdauf et al. who in their series of 101 neonates of EA found that the need for mechanical ventilation increased the odds for mortality by 2.9 times. Higher risk neonates (those with the American Society of Anesthesiologists >3 and neonates with hemodynamic instability and shock) often need inotropic support and ventilation as was also seen in the current study., A multicenter study from USA (n = 2967 surgical newborns) also identified that the use of inotropes increases the risk for mortality by 2.6 times. Enteral fed babies have significantly lower septic complications as compared to those on parental nutrition. It is postulated that enteral feeding maintains normal epithelial barrier functions and biliary concentration of secretory IgA which is an integral part of mucosal immunity. In this study, although the mean time taken to achieve full enteral nutrition did not vary significantly between the two groups, yet mortality was much higher (73%) in those where full enteral nutrition could not be achieved even beyond 14 days. Based on the findings of this study we propose the following risk stratification for surgical newborns with a minimum score of 7 and maximum of 14.
However, this shall need further studies for validation and testing.
We would like to conclude by saying that the predictor of NSM in this study unlike the previously reported series provided a more holistic assessment of patients' characteristic, surgical skill, and available infrastructure support. In addition, the predictors of NSM were simple, easy to define and record and were capable of grading the severity of the risk. NSM in this study was largely dependent on intraoperative stress factors and postoperative care. Needless to say, neonatal surgery requires expertise and special training to minimize the duration of surgery and reoperations which have a direct impact on NSM, as was demonstrated in this study. Moreover, babies with LBW, prematurity and with ISS ≥5 should be attended by the most experienced members of the surgical and anesthetist team, and the surgical procedures may be staged to decrease the surgical stress. The four factors identified as predictors of NSM in this series are modifiable and are not innate patient characteristics. We strongly believe that provision of well-equipped NICU is thus mandatory to improve postoperative care and decrease NSM. Creating awareness by proper audit and documentation of results as done in this study shall help to convince health care providers that NSM in our setting contributes significantly to neonatal mortality and needs urgent attention.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]